Unlocking natural behaviour studies with standard two-photon microscopes

Objective

Two-photon (2P) microscopy is one of the most widely used tools in neuroscience to study neuronal activity with single-cell resolution. Yet, current 2P systems are largely restricted to head-fixed animals, limiting the scope of behavioural studies. To overcome this barrier, we have recently developed a novel fiber-based miniaturized approach that enables high-resolution 2P optical studies in freely moving animals. This proposal aims to transform this innovation into a robust, user-friendly platform that can be easily disseminated, thereby widening access to freely moving 2P experiments. Our objective is to design and assemble a compact fiber-based module and validate its functionality and potential through proof-of-principle neuroscience experiments in freely moving behavioural paradigms. In parallel, we will establish an intellectual property strategy and engage with industrial partners to accelerate commercialization. By enabling widespread access to naturalistic behavioral studies, this technology will expand experimental possibilities, allow institutions to upgrade existing equipment at reduced cost, open new product lines for industry, and ultimately advance understanding of brain function and neurological disorders.